This K award will allow me to develop as an independent investigator, focusing on the role that paternal factors play in the risk of schizophrenia in offspring, specifically paternal reproductive health. The proposed program includes research and training in the translation of findings from (1) observational studies into basic experiments through collaborative efforts using animal models and (2) from experimental data into testable hypotheses using epidemiology. The training activities build on my prior experience in psychiatric epidemiology and toxicology, including coursework and research training in neuroscience and experimental animal studies. The skills that I acquire will be directly applicable to the study of many kinds of exposures relevant to schizophrenia. The research program described in this application is based on new findings that prenatal and pre-conceptual exposure that affect paternal reproductive health, including advanced paternal age and exposure to lead (Pb), a known toxin may increase susceptibility to schizophrenia and other psychotic disorders in offspring. Lead exposure results in reductions in fertility in both men and women, and is associated with behavioral abnormalities in animal models of paternal exposure. Two phases of research are proposed that will involve parallel career development activities in both training and research: (I) studies of behavioral phenotypes congruent with schizophrenia using mouse models of paternal lead exposure and advanced paternal age and (II) epidemiologic studies of paternal Pb exposure and SSD. At the conclusion of this award I will design of new collaborative programs, incorporating lifecourse epidemiology and basic research with the goal of submitting an R01 application. [unreadable] [unreadable] [unreadable] [unreadable]